Sýklódextrín nanóagnir fyrir augnlyfjagjöf

Ocular drug delivery is very challenging due to the anatomical and physiological barriers of the eye. Poor aqueous solubility of many drugs and short retention time at ocular surfaces makes the formulation of topical dosage forms even more challenging. Several approaches have been reported to enhance drug bioavailability at the ocular tissues. Cyclodextrin-based nanocarriers have been selected due to their well-known capability of cyclodextrins to enhance the solubility of lipophilic drugs and its permeability through biological membranes. They can also prolong the retention time of ophthalmic formulations on the ocular surface and, as a consequence, increase their bioavailability. The aim of this project was to apply cyclodextrin technology and cyclodextrin-amphiphilic copolymers to enhance the aqueous solubility of two poorly soluble drugs, Nepafenac and Natamycin, as well as their corneal or scleral accumulation. Nepafenac is a non-steroidal anti-inflammatory drug (NSAID) prescribed for the treatment of pain and inflammation that usually occurred after cataract surgery. Nepafenac has low water solubility and ocular permeability. The complexation of nepafenac with six CDs and various water-soluble polymers was investigated. Results showed that HPβ-CD showed the highest solubilizing capacity, while γ-CD led to the highest aggregate formation. Complex formation was investigated and supported by phase solubility analysis, DSC, FT-IR and ¹H-NMR. The optimized complex, which contained 15% (w/v) γ-CD and 8% (w/v) HPβ-CD, was selected for additional studies. Nine formulations containing nepafenac/γ-CD/HPβ-CD complexes and various water-soluble polymers were prepared. Physicochemical and rheological characterization, mucoadhesive capacity, ocular tolerance, diffusion studies, corneal and scleral permeability, and anti-inflammatory activity of these formulations were investigated and compared to the marketed nepafenac suspension, Nevanac® 3 mg/mL. The formulations displayed zeta potential from –6 to –27 mV, microparticle size in the range of 340-5950 nm, neutral pH and high sclera permeation. Moreover, they were found to be non-toxic and non-irritant. Compared to Nevanac®, formulations containing poly(vinyl)-alcohol (PVA), methylcellulose (MC) and carboxymethyl cellulose (CMC) presented the best results in relation to sclera accumulation and anti-inflammatory activity. Natamycin is approved for the treatment of fungal keratitis but its use is restricted due to its low water solubility and low ocular penetration. Soluplus® and Pluronic® P103 were selected as surfactants to prepare single and mixed micelles and poly(pseudo)rotaxanes for Natamycin encapsulation. Soluplus, Pluronic P103 and a mixture of Soluplus/ Pluronic in ratio 4:1 dispersions were prepared with and without 10% α-CD in 0.9% sodium chloride or buffer pH 6.4. They were investigated in relation to their solubility, particle size, zeta potential, pH, rheological properties, diffusion studies, ocular irritancy, and ex vivo cornea and sclera permeation. All formulations revealed zeta potentials close to zero while differences were found with respect to their size. Soluplus micelles and mixed micelles revealed larger sizes (range 90-150 nm) followed by Pluronic P103 micelles. Soluplus micelles led to the highest Natamicyn solubility, followed by Pluronic P103 and their mixed micelles. All formulations were found cytocompatible on murine fibroblasts and did not display irritation. Although Soluplus nanomicelles and poly(pseudo)rotaxanes showed in situ gel behavior at 35 ºC and the highest solubilizing capacity, Pluronic and Soluplus poly(pseudo)rotaxanes led to the lowest diffusion rate and corneal and sclera permeation. Moreover, poly(pseudo)rotaxanes of mixed micelles showed intermediate diffusion release and permeability through cornea and sclera comparing to only Soluplus and Pluronic poly(pseudo)rotaxanes. To conclude, we would like to point out that both optimized Nepafenac formulation and Natamycin-based mixed poly(pseudo)rotaxanes may represent a new approach for topical instillation of drugs to the posterior segment of the eye

COMPARISON OF THE SWIMMING START PERFORMANCE BETWEEN INDIVIDUAL AND RELAY FREESTYLE RACES

The aim of the present study was to compare the swimming start performances between individual and relay events in freestyle races. Competitors who took part in both the individual 100m freestyle and the 4×100m freestyle relay races during the LEN 2017 European Junior Championships were analysed in the present study. The results indicated that swimmers performed 6.92% faster 15m start time in relay race versus the individual freestyle race and the difference seemed to be due to the longer reaction time from the race beginning. Coaches and swimmers would be suggested to try to optimize their relay starting performance in order to take more benefit on flight, underwater and swimming phases compare to individual start

In Vitro and Ex Vivo Evaluation of Nepafenac-Based Cyclodextrin Microparticles for Treatment of Eye Inflammation

The aim of this study was to design and evaluate novel cyclodextrin (CD)-based aggregate formulations to efficiently deliver nepafenac topically to the eye structure, to treat inflammation and increase nepafenac levels in the posterior segment, thus attenuating the response of inflammatory mediators. The physicochemical properties of nine aggregate formulations containing nepafenac/γ-CD/hydroxypropyl-β (HPβ)-CD complexes as well as their rheological properties, mucoadhesion, ocular irritancy, corneal and scleral permeability, and anti-inflammatory activity were investigated in detail. The results were compared with a commercially available nepafenac suspension, Nevanac® 3 mg/mL. All formulations showed microparticles, neutral pH, and negative zeta potential (–6 to –27 mV). They were non-irritating and nontoxic and showed high permeation through bovine sclera. Formulations containing carboxymethyl cellulose (CMC) showed greater anti-inflammatory activity, even higher than the commercial formulation, Nevanac® 0.3%. The optimized formulations represent an opportunity for topical instillation of drugs to the posterior segment of the eyeThis research was funded by MINECO (SAF2017-83118-R), Agencia Estatal de Investigación (AEI) Spain, Xunta de Galicia (ED431C 2016/008), and FEDER (Spain). B.L.-V. acknowledges an Erasmus+ traineeship (IS-SM2018-81075)S

Detección de personas en riesgo de padecer diabetes en farmacias comunitarias españolas

Objetivo: Detectar personas con riesgo alto/muy alto de padecer diabetes y derivarlas al médico, evaluar en la muestra la prevalencia de los distintos factores de riesgo y realizar una intervención educativa mínima sobre éstos en todos los usuarios participantes.Material y métodos: Estudio observacional transversal realizado en noviembre de 2014. Se incluyeron usuarios de la farmacia, mayores de 18 años, no diagnosticados de diabetes y que aceptaron realizar la encuesta. Muestreo no probabilístico.Variable principal: puntuación obtenida en el cuestionario Findrisc. Otras: características demográficas, IMC, perímetro de cintura, glucemia capilar (si F≥15), medicación, intervención, tiempo empleado.Resultados: Participaron 90 farmacéuticos de las 17 comunidades autónomas. Realizaron 1.520 cuestionarios Findrisc. La puntuación media de la muestra fue de 10,9 (DE=5,1). El número de individuos con riesgo alto o muy alto fue de 370 (24,3%) de los 1.520 encuestados. 207, el 55,9% de aquellos y el 13,6% de la muestra total, tenían glucemia ≥110 mg/dL y se derivaron al médico. Existe relación directa entre el número de medicamentos utilizados y el riesgo de diabetes. El tiempo empleado en la intervención fue de 9,9 (DE=5,1) minutos.Conclusiones: El alto porcentaje de participantes con riesgo alto/muy alto de padecer diabetes que son derivados al médico de familia para valorar su situación, avala la eficiencia de la farmacia en este tipo de cribados. La intervención educativa realizada con los participantes supone una llamada de atención sobre la importancia del estilo de vida saludable orientado a la prevención de las enfermedades metabólicas

Actualidad de las Plantas Medicinales en Terapéutica

RESUMENLas plantas medicinales han sido utilizadas por el hombre desde tiempo inmemorial para el alivio o curación de sus enfermedades. En la actualidad no solo se utilizan como punto de partida para la obtención de medicamentos industriales sino que mantienen plena vigencia para el tratamiento de numerosas dolencias. A pesar de su origen natural no están exentas de riesgos para la salud pues algunas provocan reacciones adversas e interacciones con otros fármacos que hay que tener en cuenta.En el presente trabajo se repasan las principales plantas medicinales, de gran utilidad terapéutica y amplio uso, clasificadas de acuerdo con los sistemas funcionales sobre los que actúan.Palabras claveFitoterapia, medicamentos, acción farmacológica, principios activos, interacciones medicamento-planta medicinal. ABSTRACTMedicinal plants have been used for the relief or cure of several diseases for centuries. Most of the medicines we used today are derived straight from plants and medicinal plants are used as a drug themselves, with great utility in therapeutics. Despite their natural origin, herbal drugs are not free of side effects or interactions with other drugs that must be taken into account.This study review the efficacy and safety of the most used medicinal plants classified according to the functional systems where they act.Key words:Phytotherapy, medicines, pharmacological action, active principles, interactions drug-medicinal plant

Characteristics and outcomes of adult patients in the PETHEMA registry with relapsed or refractory FLT3-ITD mutation-positive acute myeloid leukemia

This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant.This study was supported by Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Valencia, Spain [CB16/12/00284]

Acute leukemia arising from myeloproliferative or myelodysplastic/myeloproliferative neoplasms: A series of 372 patients from the PETHEMA AML registry

PETHEMA group.Treatment of acute myeloid leukemia (AML) evolving from myeloproliferative (MPN) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) is challenging. We evaluated disease characteristics, treatment patterns and outcomes in 372 patients diagnosed with AML after MPN or MDS/MPN over a 27-year period. Frontline treatment was intensive chemotherapy (38%), hypomethylating agents [HMAs] (17%), non-intensive chemotherapy (14%), and supportive care (31%). Median overall survival was 4.8 months, with a 5-year survival rate of 4%. Median survival was 2.8, 3.9 and 8.3 months for the 1992-2010, 2011-2015 and 2016-2019 periods, respectively (test for trend p < 0.001). Complete response (CR) rate was higher with intensive chemotherapy (43%) than with non-intensive chemotherapy (12%) or HMAs (8.5%) [p < 0.001], but responses were short-lived without allogeneic hematopoietic cell transplantation. Patients treated with intensive chemotherapy or HMAs had superior survival than those receiving non-intensive chemotherapy (median: 8.5 vs. 8.6 vs. 4.2 months, respectively). No differences in treatment response or survival were observed according to prior disease subtypes. Patients undergoing transplantation in CR had better survival than those transplanted in other response categories (3-year survival rate of 64% vs. 22%, p = 0.002). Our results support the use of intensive chemotherapy followed by transplant whenever possible, and the preferential use of HMAs over attenuated chemotherapy regimens in unfit patients. In spite of the survival improvement in recent years, this subset of AML constitutes an unmet medical need and deserves systematic incorporation in clinical trials.Peer reviewe

Cyclodextrin–Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin

Natamycin is the only drug approved for fungal keratitis treatment, but its low water solubility and low ocular penetration limit its efficacy. The purpose of this study was to overcome these limitations by encapsulating the drug in single or mixed micelles and poly(pseudo)rotaxanes. Soluplus and Pluronic P103 dispersions were prepared in 0.9% NaCl and pH 6.4 buffer, with or without α-cyclodextrin (αCD; 10% w/v), and characterized through particle size, zeta potential, solubilization efficiency, rheological properties, ocular tolerance, in vitro drug diffusion, and ex vivo permeation studies. Soluplus micelles (90–103 nm) and mixed micelles (150–110 nm) were larger than Pluronic P103 ones (16–20 nm), but all showed zeta potentials close to zero. Soluplus, Pluronic P103, and their mixed micelles increased natamycin solubility up to 6.00-fold, 3.27-fold, and 2.77-fold, respectively. Soluplus dispersions and poly(pseudo)rotaxanes exhibited in situ gelling capability, and they transformed into weak gels above 30 °C. All the formulations were non-irritant according to Hen’s Egg Test on the Chorioallantoic Membrane (HET-CAM) assay. Poly(pseudo)rotaxanes facilitated drug accumulation into the cornea and sclera, but led to lower natamycin permeability through the sclera than the corresponding micelles. Poly(pseudo)rotaxanes made from mixed micelles showed intermediate natamycin diffusion coefficients and permeability values between those of Pluronic P103-based and Soluplus-based poly(pseudo)rotaxanes. Therefore, the preparation of mixed micelles may be a useful tool to regulate drug release and enhance ocular permeabilityThis research was funded by MINECO [SAF2017-83118-R], Agencia Estatal de Investigación (AEI) Spain, Xunta de Galicia (Grupo de Referencia Competitiva ED431C 2016/008; Agrupación Estratégica en Materiales-AEMAT ED431E 2018/08), and FEDER (Spain). B.L.-V. acknowledges an Erasmus+ traineeship (IS-SM2018-81075)S

Nepafenac-Loaded Cyclodextrin/Polymer Nanoaggregates: A New Approach to Eye Drop Formulation

The topical administration route is commonly used for targeting therapeutics to the eye; however, improving the bioavailability of drugs applied directly to the eye remains a challenge. Different strategies have been studied to address this challenge. One of them is the use of aggregates that are formed easily by self-assembly of cyclodextrin (CD)/drug complexes in aqueous solution. The aim of this study was to design a new eye drop formulation based on aggregates formed between CD/drug complexes. For this purpose, the physicochemical properties of the aggregates associated with six CDs and selected water-soluble polymers were analysed. Complex formation was studied using differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and 1H nuclear magnetic resonance spectroscopy (1H-NMR). Results showed that HP&beta;CD performed best in terms of solubilization, while &gamma;CD performed best in terms of enhancing nanoaggregate formation. Formation of inclusion complexes was confirmed by DSC, FT-IR and 1H-NMR studies. A mixture of 15% (w/v) &gamma;CD and 8% (w/v) HP&beta;CD was selected for formulation studies. It was concluded that formulations with aggregate sizes less than 1 &micro;m and viscosity around 10&ndash;19 centipoises can be easily prepared using a mixture of CDs. Formulations containing polymeric drug/CD nanoaggregates represent an interesting strategy for enhanced topical delivery of nepafenac

Comparison of starts and turns between individual and relay swimming races

The present study investigated swimmers’ performances on the starting and turning segments between individual and relay races. A total number of 72 race performances of the same swimmers in both relay 4 × 100 m finals (freestyle, medley, and mixed freestyle) and individual 100 m finals or semi-finals (butterfly, breaststroke, and freestyle) from the LEN European Swimming Championships were compared with repeated measures MANOVA. Swimmers performed 5–7% faster starts in the relay than in the corresponding individual events, despite no differences in the flight phase and a lower performance (shorter distances and slower velocities) on the underwater start section. The 15 m turn times were slower in the butterfly relay races although no specific differences in the underwater parameters were observed. These results suggest that specific training of the starting and turning segments should be performed under relay conditions to optimise pacing and performance in the underwater sections